S. Messer

Normothermic donor heart perfusion: current clinical experience and the future

Following the first successful heart transplant in 1967, more than 100 000 heart transplants have been carried out worldwide. These procedures have mostly relied on cold ischaemic preservation of the donor heart because this simple technique is inexpensive and relatively reliable. However, the well‐known limitations of cold ischaemic preservation imposes significant logistical challenges to heart transplantation which put a ceiling on the immediate success on this life‐saving therapy, and limits the number of donor hearts that can be safely transplanted annually. Although the theoretical advantages of normothermic donor heart perfusion have been recognised for over a century, the technology to transport donor hearts in this state has only been developed within the last decade. The Organ Care System (OCS) which is designed and manufactured by TransMedics Inc. is currently the only commercially available device with this capability. This article reviews the history of normothermic heart perfusion and the clinical experience with the TransMedics OCS to date. We have also attempted to speculate on the future possibilities of this innovative and exciting technology.

Functional assessment and transplantation of the donor heart after circulatory death

BACKGROUND After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program. METHODS Normothermic regional perfusion (NRP) was used to restore function to the arrested DCD heart within the donor after exclusion of the cerebral circulation. After weaning from support, DCD hearts underwent functional assessment with cardiac-output studies, echocardiography, and pressure-volume loops. In the feasibility phase, hearts were transported perfused before evaluation of function in modified working mode extracorporeally. After the establishment of a reliable assessment technique, hearts with demonstrable good function were then selected for clinical transplantation. RESULTS NRP was instituted in 13 adult DCD donors, median age of 33 years (interquartile range [IQR], 28-38 years), after a median ischemic time from withdrawal to perfusion of 24 minutes (IQR, 21-29; range, 17-146 minutes). Two of 4 hearts in the feasibility phase were unsuitable for transplantation after functional assessment. Nine DCD hearts were transplanted in the clinical phase, with 100% survival. The median intensive care duration was 5 days (IQR, 4-5 days), with 2 patients requiring mechanical support. There were no episodes of rejection (total, 1,436 patient-days; range, 48-297). During the same period, we performed 20 standard heart transplants using brain-dead donors. CONCLUSIONS NRP allows rapid reperfusion and functional assessment of the DCD donor heart, ensuring only viable hearts are selected for transplantation. This technique minimizes the risk of primary graft dysfunction and maximizes confidence in DCD heart transplantation, realizing a 45% increase in our heart transplant activity.

Resuscitating heart transplantation: the donation after circulatory determined death donor.

Despite advances in mechanical support, heart transplantation still remains the gold standard treatment for end-stage drugresistant heart failure. It provides both excellent long-term survival and a near-normal quality of life. Unfortunately, as the number of patients eligible for heart transplantation continues to rise, the number of suitable donors after brain death (DBD) continues to fall. In the UK, this increasing disparity between demand and supply results in less than half of patients being transplanted while 43% of the waiting list are either permanently removed or die waiting for a heart transplant [1]. With the heart transplant waiting list increasing at a rapid rate (Fig. 1), attention has fallen on extended criteria donors. In Europe, it is now routine to consider those hearts from donors up to 65 years old, those with ventricular hypertrophy or those with a history of prolonged cardiac arrest. However, even after incorporating these marginal donors, there remains an increasing shortfall in meeting demand. In an attempt to push the boundaries still further, some enthusiasts, including Tolboom et al. in this edition, are looking towards the donation after circulatory determined death (DCD) donor to bridge the gap. DCD donors are patients who have sustained catastrophic brain injury but who will not proceed to brain stem death or where brain stem testing would be inappropriate. After consultation between the intensive care doctors and the family, a decision to withdraw therapy is made after it has been established that it would be futile to continue and not in the best interests of the patient.

Early Results Using Donation After Circulatory Death (DCD) Donor Hearts

Donation after circulatory death (DCD) has contributed significantly to kidney, lung and liver transplant activities over the last decade. With an ever increasing demand for cardiac transplantation and worsening shortages of donor hearts, there has been growing interests in transplanting hearts from DCD donors. This was initially made possible by co-locating the donor and recipient to ensure the shortest possible ischaemic time for the DCD heart. More recently, reconditioning and distant procurement of arrested DCD hearts has been achieved by using machine perfusion. Early outcomes have been very encouraging, and experience to date suggests that DCD donors can contribute significantly to the number of donor hearts available for transplantation. There are variations in the legal and ethical frameworks between countries with regard to DCD organ donation and transplant teams must work within their respective local guidelines. We review the current status of clinical DCD heart transplantation and appraise the merits of the various approaches.

Clinical and ethical challenges in heart transplantation from donation after circulatory determined death donors

Purpose of review The aim of this study was to describe the development of a clinical programme of heart transplantation from nonheart beating (or donation after circulatory determined death, DCD) donors. DCD is an established practice in abdominal and lung transplantation. The opportunity for sufferers of advanced heart failure provided by DCD heart transplantation is described. Recent findings Work shows that the arrested DCD heart is viable and has a 30-min tolerance to anoxia at normal body temperature making transplantation possible. Summary The demonstration of the possibility of DCD heart transplantation and its early clinical success is described.

Ventriculo‐arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease

Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP) <25 mmHg at rest in patients that remain symptomatic from chronic pulmonary artery thrombi. To improve identification of right ventricular (RV) pathology in patients with thromboembolic obstruction, we hypothesized that the RV ventriculo‐arterial (Ees/Ea) coupling ratio at maximal stroke work (Ees/Eamax sw) derived from an animal model of pulmonary obstruction may be used to identify occult RV dysfunction (low Ees/Ea) or residual RV energetic reserve (high Ees/Ea). Eighteen open chested pigs had conductance catheter RV pressure‐volume (PV)‐loops recorded during PA snare to determine Ees/Eamax sw. This was then applied to 10 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and ten patients with CTED, also assessed by RV conductance catheter and cardiopulmonary exercise testing. All patients were then restratified by Ees/Ea. The animal model determined an Ees/Eamax sw = 0.68 ± 0.23 threshold, either side of which cardiac output and RV stroke work fell. Two patients with CTED were identified with an Ees/Ea well below 0.68 suggesting occult RV dysfunction whilst three patients with CTEPH demonstrated Ees/Ea ≥ 0.68 suggesting residual RV energetic reserve. Ees/Ea > 0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively, P = 0.006) and higher end‐systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively, P < 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction.

Human heart transplantation from donation after circulatory-determined death donors using normothermic regional perfusion and cold storage

Heart transplantation from donation after circulatory-determined-death (DCD) donors is emerging as an additional avenue to increase heart transplant activity. Previous methods of DCD heart retrieval include direct procurement and cold storage, direct procurement, and machine perfusion and normothermic regional perfusion, followed by machine perfusion during transportation. Herein we report a further technique resulting in successful DCD heart transplantation utilizing normothermic regional perfusion and permitting functional assessment followed by cold storage.

Better Graft Survival with no Ischemic Cholangiopathy in DCD Liver Transplantation in the UK using Normothermic Regional Perfusion (NRP)

Background Normothermic regional perfusion, whereby the donor is placed on an extracorporeal circuit to circulate oxygenated blood to the abdominal viscera after death, is increasingly being used in controlled donation after circulatory death (DCD) donation. We evaluated the joint experience of the two centres pioneering this technique in the UK and compared NRP DCD liver transplants to non-NRP DCD livers transplanted at each centre in the same period. Methods Between 1/1/2011 and 31/5/17, 44 patients underwent liver transplantation following NRP; these were compared to 185 DCD liver transplants without NRP performed in the same period. NRP was performed for a median 123 (IQR 101-130) minutes before in-situ cold perfusion. Results Table 1 summarises the results. There was no significant difference in the recipient age (58 vs 61) or UK End Stage Liver disease (UKELD) score (55.7 NRP vs 54.3 non-NRP) between groups. 90 day patient survival was similar (100% NRP vs 96.7% non-NRP). There was a significant reduction in ischemic cholangiopathy and early allograft dysfunction with a better graft survival at 90 days. Conclusion Livers from DCD donors undergoing NRP have a lower incidence of primary non function and early allograft dysfunction, fewer biliary complications, and significantly better early graft survival. Table. No title available.

Transplantation of Hearts Donated after Circulatory Death

Cardiac transplantation has become limited by a critical shortage of suitable organs from brain-dead donors. Reports describing the successful clinical transplantation of hearts donated after circulatory death (DCD) have recently emerged. Hearts from DCD donors suffer significant ischemic injury prior to organ procurement; therefore, the traditional approach to the transplantation of hearts from brain-dead donors is not applicable to the DCD context. Advances in our understanding of ischemic post-conditioning have facilitated the development of DCD heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement. The availability of a clinically approved ex situ heart perfusion device now allows DCD heart preservation in a normothermic beating state and minimizes exposure to incremental cold ischemia. This technology also facilitates assessments of organ viability to be undertaken prior to transplantation, thereby minimizing the risk of primary graft dysfunction. The application of a tailored approach to DCD heart transplantation that focuses on organ resuscitation at the time of procurement, ex situ preservation, and pre-transplant assessments of organ viability has facilitated the successful clinical application of DCD heart transplantation. The transplantation of hearts from DCD donors is now a clinical reality. Investigating ways to optimize the resuscitation, preservation, evaluation, and long-term outcomes is vital to ensure a broader application of DCD heart transplantation in the future.

Lung donation after circulatory determined death: a single-centre experience†

OBJECTIVES Donor organ utilization and shortage remain the major limitations to the opportunity of a lung transplantation (LTx). Donation after circulatory determined death (DCD) has been adopted as a source of additional organs worldwide. However, concerns about organ quality and ischaemia-reperfusion injury have limited its application. The aim of this study was to retrospectively analyse a single-centre experience in the DCD LTx and compare early and mid-term outcomes with those from a standard donation after brain death (DBD). METHODS During the 6-year study period, 186 LTxs were performed: 147 bilateral LTxs (79%) and 39 single LTxs (21%). Of these, 23 recipients received organs retrieved from DCD donors (12.4%). RESULTS No differences were found between the 2 groups of recipients except for age and cystic fibrosis as an underlying disease. No differences in terms of duration of mechanical ventilation, incidence of postoperative extracorporeal membrane oxygenation support, intensive care unit stay, hospital length of stay, airway anastomotic complications, incidence and grade of rejection and freedom from bronchiolitis obliterans syndrome were demonstrated. There was a non-statistically significant trend towards older age in the DCD group. Actuarial survival in the subgroup of bilateral LTx at 1 year and 5 years was 75% and 51% for the DCD group and 82% and 61% for the DBD group, respectively (P = 0.12). CONCLUSIONS Short- and medium-term outcomes after the DCD LTx are comparable with those achieved after transplantation from the DBD donors, despite a tendency to use DCD lungs for older recipients. Therefore, the DCD LTx is a clinical option that can be used with favourable results to expand the lung donor pool.